IthaID: 1182


Names and Sequences

Functionality: Globin gene causative mutation
Common Name: CD 112 TGT>CGT [Cys>Arg] HGVS Name: HBB:c.337T>C
Hb Name: Hb Indianapolis Protein Info: β 112(G14) Cys>Arg

Context nucleotide sequence:
ACAGCTCCTGGGCAACGTGCTGGTC [C/T] GTGTGCTGGCCCATCACTTTGGCAA (Strand: -)

Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVRVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Comments: Cysteine at position β112 (G14) is an internal residue in the central cavity and participates in the α1β1 interactions throught contact with the α107 (G14)Val, α110 (G17)Ala, and α122 (H5)His residues. Replacement of the hydrophobic cysteine by a larger, polar arginine probably leads to an inadequate adaptation that causes some degree of instability. Initially reported in a heterozygous state in a family with a severe, dominantly inherited β-thalassemia phenotype. Extremely unstable variant; its identity could only be studied by biosynthetic analysis in which a radio-active abnormal peak was observed [PMID: 429365, 447835]. Later reported in families from Spain [PMID: 3781865] and Italy [PMID: 3170235] with a benign clinical image; no anaemia with only a slight reticulocytosis. Variant was mildly unstable (~40% of the total β-globin). Reported in a Brazilian patient with moderate anaemia, mild reticulocytosis and acute renal failure. Instability tests (heat, isopropanol, and n-butanol) and Heinz body tests were all positive [PMID: 17211844]. To address this phenotypic discrepancy, further investigation of the original family by DNA sequencing revealed the presence of a different mutation in the β-globin gene; the variant was renamed to Hb Terre Haute [IthaID: 230] [PMID: 2005117].

Location

Chromosome: 11
Locus: NG_000007.3
Locus Location: 71911
Size: 1 bp
Located at: β
Specific Location: Exon 3

Phenotype

Hemoglobinopathy Group: Structural Haemoglobinopathy
Hemoglobinopathy Subgroup: β-chain variant
Allele Phenotype:N/A
Stability: Unstable
Oxygen Affinity: N/A
Associated Phenotypes: N/A

Other details

Type of Mutation: Point-Mutation(Substitution)
Effect on Gene/Protein Function: N/A
Ethnic Origin: Brazilian
Inheritance: Dominant
DNA Sequence Determined: Yes
Detection Methods: Direct DNA sequencing

Publications / Origin

  1. Adams JG, Steinberg MH, Boxer LA, Baehner RL, Forget BG, Tsistrakis GA, The structure of hemoglobin Indianapolis [beta112(G14) arginine]. An unstable variant detectable only by isotopic labeling., The Journal of biological chemistry, 254(9), 3479-82, 1979
  2. Adams JG, Boxer LA, Baehner RL, Forget BG, Tsistrakis GA, Steinberg MH, Hemoglobin Indianapolis (beta 112[G14] arginine). An unstable beta-chain variant producing the phenotype of severe beta-thalassemia., J. Clin. Invest., 63(5), 931-8, 1979
  3. Baiget M, Gomez Pereira C, Jue DL, Johnson MH, McGuffey JE, Moo-Penn WF, A case of hemoglobin Indianapolis [beta 112(G14) Cys----Arg] in an individual from Cordoba, Spain., Hemoglobin, 10(5), 483-94, 1986
  4. De Biasi R, Spiteri D, Caldora M, Iodice R, Pucci P, Malorni A, Ferranti P, Marino G, Identification by fast atom bombardment mass spectrometry of Hb Indianapolis [beta 112(G14)Cys----Arg] in a family from Naples, Italy., Hemoglobin, 12(4), 323-36, 1988
  5. Coleman MB, Steinberg MH, Adams JG, Hemoglobin Terre Haute arginine beta 106. A posthumous correction to the original structure of hemoglobin Indianapolis., The Journal of biological chemistry, 266(9), 5798-800, 1991
  6. Fattori A, Kimura EM, Albuquerque DM, Oliveira DM, Costa FF, Sonati MF, Hb Indianapolis [beta112 (G14) Cys-->Arg] as the probable cause of moderate hemolytic anemia and renal damage in a Brazilian patient., Am. J. Hematol., 82(7), 672-5, 2007
Created on 2010-06-16 16:13:17, Last reviewed on 2019-06-24 14:49:58 (Show full history)

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